Long-lasting, immunologically specific suppression ("enhancement") of rat renal allograft rejection has been achieved by treatment of the recipient with donor antigen and anti-donor alloantibody. Recent evidence suggests that production of anti-idiotypic antibody against idiotypic determinants in the enhancing serum may be important in the specific suppression of rat renal allograft rejection produced by treatment in this fashion with alloantigen and antibody. The conceptual basis is straight forward: an antigenic determinant selects and stimulates B lymphocytes having immunoglobulin receptors which combine with it specifically. These cells proliferate and synthesize antibody, the combining site of which is similar to or identical with that of the receptor immunoglobulin. The combining region of an antibody is potentially antigenic and, under appropriate circumstances, stimulates production of anti-idiotypic antibody reactive with idiotypic determinants in the combing region. This anti-idiotypic antibody can also bind to receptor for antigen on lymphoid cells. Anti-idiotypic antibody has been found to suppress antibody response to alloantigen in adult rats and to inhibit graft-versus-host reactivity of lymphoid cells specifically. The objectives of the proposed studies are: to determine the immunological reactivity of sera and lymphocytes from rats immunized to produce anti-idiotypic antibody, to determine immunological reactivity of sera and lymphocytes from rats bearing enhanced renal allografts, to determine the effect of anti-idiotypic antibody and lymphocytes on the specific selection of recirculating lymphocytes, and to devise ways of overcoming specific suppression. The ultimate goals are to develop rational and effective approaches that will be useful clinically in obtaining indefinite survival of organ and tissue allografts or in achieving rejection of progressively growing tumors.